Diabetes mellitus by Dr/Amr Gawaly Assistant Lecture Internal Medicine Department Tanta University hospitals
Screening for Diabetes • All adults over 45 years of age. • If blood glucose normal and no risk factors present, retest in 3 years • Test younger adults if overweight (BMI > 25) and have at least one of the following risk factors: • Physically inactive most of the time. • Parent, brother or sister with diabetes. • Hypertensive (>140/90 mmHg). • HDL <35 mg/dl and/or fasting triglycerides >250 mg/dl. • History of vascular disease. • Woman with history of gestational diabetes. • delivery of baby over 9 pounds. • Have polycystic ovary syndrome. • Previously diagnosed with impaired glucose toleranceor impaired fasting glucose.
Criteria for Screening for Type 2 Diabetes in Children: • Overweight (classified by any of the following). • BMI > 85 percentile for age and sex. • Weight for height > 85 percentile. • Weight > 120% ideal for height. Plus • any two of the following risk factors: • Parent, brother or sister with type 2 diabetes. • Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia or polycystic ovary syndrome). • Screening should be done at age 10 or at the onset of puberty and repeated every 2 years.
Diagnosis of Diabetes Nonpregnant adults and children • Fasting plasma glucose >126 mg/dl (Preferred method). • postprandial plasma glucose >200 mg/dl plus classic symptoms (increased urination, increased thirst, weight loss). • 100 gram oral glucose tolerance test: 2 hour reading >200 mg/dl. • All methods need to confirmed on a subsequent day. • Finger prick tests and HbA1c are not recommended tests for diagnosing diabetes.
Gestational Diabetes • At 24-28 weeks, after 8 hour fast 100 gram glucose tolerance test. • glucose test >140 mg/dl after 3 hour administrator. • 2 or more abnormal values during oral glucose tolerance test (100 g, 3 hour test) is diagnostic of gestational diabetes Normal values, 3 hour glucose tolerance test: • Time (hours) Venous plasma values (mg/dl) 0 95 1 180 2 155 3 140 American Diabetes Association (2003). Clinical Practice Recommendations, 2003. Diabetes Care, Vol 26 (1).
Clinical Practice Recommendations To Do At Every Visit • Check blood pressure. • Assess hypoglycemia - frequency, possible causes, and severity. • Review self-monitored blood glucose values. • Discuss adherence to treatment plan. • Look for symptoms associated with diabetes related complications. • Visually inspect feet (The practice of foot exams at every office visit has been shown to reduce the rate of amputations by 50%).
Clinical Practice RecommendationsTo do Quarterly/Annually at every visit Twice per year
To do Quarterly/Annually As indicated As indicated
Impotents notes • Dilated eye exam In Type 1 within 3-5 years of onset of diabetes, then annually. • Lipid profile • in children with type 1 over age 12: at diagnosis when blood glucose is under control. • If normal, then every 5 years until age 18, then annually. • Children with type 2: at diagnosis when blood glucose under control. If normal, repeat every 2 years. • Urine analysis in Type 1: only after puberty has started and have had diabetes for at least 5 years. • Serum creatinine in children: only ones with proteinuria. • Thyroid problems are more prevalent with type 1 diabetes.
Management Plan for Diabetes • nutrition plan and instructions. • Medication review (include prescription, non-prescription and herbal medications). • Instructions on when to contact the physician. • Dental hygiene. • Recommendations for lifestyle changes (meal planning, activity, smoking cessation). • Women of childbearing age; discussion of contraceptives and need for optimal blood glucose control prior to conception. • Referral for dilated eye exam
Nutrition and Diabetes • The majority of people with diabetes are overweight, a small amount of weight loss (5-9 kg) can greatly assist with glycemic control, even if the person does not attain a desirable body weight. In General, People with Diabetes... • Do not need any special diet foods (Some of the reduced calorie items can be useful). • High fiber foods such as dried beans, fruits, vegetables and whole grains everyday. • limit the amount of saturated fat and hydrogenated fat consumed - found in animal products such as cheese, hamburger, butter. • Eating on a regular basis (every 4-5 hours). • Need to eat consistent amounts of carbohydrates (from fruit, milk, bread/starch, and sweets) at meals.
Sugar and Diabetes • Most people with diabetes can also include some sugar in their meal plan. The sugar containing food must be substituted for some of the other carbohydrate (bread and starches, fruits, vegetables or milk) • Sugar-free Products • Sugar-free products are not all reduced calorie items. If it contains aspartame, saccharin, or sucralose, the calorie and carbohydrate content will be lower than the regular product, and it may be useful for the person with diabetes. • If the item is sweetened with fruit juice, honey, molasses, it is not a calorie-reduced product! There is no real benefit to using these products in place of sugar sweetened products. Mild caloric restrictions (250-500 calorie deficit.) assist with glycemic control.
Physical Activity and Diabetes Benefits of Regular Physical Activity for People with Diabetes • Reduces the risk of Coronary Artery Disease (Decreases plasma cholesterol, triglycerides and LDL-cholesterol, Increases HDL-cholesterol). • Assists with blood pressure control. • Improves insulin sensitivity. • Reduces hyperinsulinemia. • Reduces body fat and may assist with weight loss. • Increases muscle mass. • Improves quality of life. • Can reduce stress. • Reduce HbA1C levels • Decrease or eliminate the need for insulin or oral agents in some.
Physical Activity Recommendations Type 2 diabetes: 30 – 60 minutes up to 5 times a week. Type 1 diabetes: all levels of activity can be performed by those without complications and are in good glycemic control. For the older adult: 30-40 minutes 5-6 times a week. For weight loss: at least 60 minutes most days of the week. Activity Sessions Each activity session should begin with a couple of minutes of light activity, followed by stretching. Activity:Aerobic activity (e.g. walking, swimming or biking). Depending on fitness level, the activity session can last from 5-60 minutes.
Pharmacological Treatment of Diabetes • Patients with extremely high blood glucose and symptoms such as polyuria, and polydipsia, may need insulin to be started immediately. • Alteration of the other medications, the patient is taking may help to control blood glucose; hyperglycemia may result from nicotinic acid, thiazide diuretics (large doses), beta blockers, Indocin, Dilantin, corticosteroids and fertility agents. • After 5 years, approximately 50% of patients will require medication adjustments. • Combination therapies can be tried before discontinuing the failed drug (i.e. add metformin if person has failed with sulfonylurea to control blood glucose). • If combination therapy fails to control blood glucose, insulin is the next line of treatment
Oral therapy for type 2 diabetes • Sulfonylureas secretagogus. • Non-Sulfonylureas secretagogus. (1) Benzoic Acid Derivatives (2) D-Phenylalanine Derivatives • Biguanides. • Thiazolidinediones. • Alpha Glucosidase Inhibitors.
Sulfonylureassecretagogus • Stimulate the pancreas to make more insulin. Over time, the body’s ability to make insulin may lessen. • Fasting plasma glucose 126-200 mg/dl may respond to monotherapy alone with dietary management. • Fasting plasma glucose 200-275 mg/dl may need 2 agents or insulin. • If a sulfonylureas alone fails to control blood glucose, combination therapy or insulin may be used to achieve blood glucose control.
Sulfonylureassecretagogus • 1st Generation • Chlorporpamide (Diabinese) • Tolbutamide (Diamol) • 2nd Generation • Glibenclamide (Daonil) • Gliclazide (Diamicron) • Glipizide (minidiab) • Glimepiride (Amaryl) • Side Effects • Hypoglycemia • Weight gain • Skin rashes • Hematologic changes (1st generation drugs)
Sulfonylureassecretagogus • Dosing • Start at lowest possible dose. • Increase every 1-2 weeks until glucose control or maximum dose has been reached. • Longer-acting agents may not be recommended for the elderly. • Renal insufficiency may require dose reduction. • There is no benefit to using two sulfonylureas together. • Candidates for Initial Use • Type 2 diabetes • no dyslipidemia, not overweight, • fasting plasma glucose > 20 mg/dl above target
Sulfonylureassecretagogus Contraindications • Type 1 diabetes. • Pregnancy and lactation. • Diabetic Ketoacidosis. • Severerenal or hepatic disease. • Elderly, debilitated or malnourished persons. • Allergy to sulfa. • Serious illness/severe infection. • Surgery, trauma or severe metabolic stress.
Non-sulfonylureassecretagogus Benzoic Acid Derivative • Repaglinide (NovoNorm) • Enhances insulin secretion. • Is a short-acting agent. • The amount of repaglinide-induced insulin release depends on the blood glucose level. • Insulin release diminishes as the glucose level declines. • Has the potential to cause hypoglycemia, but to a lesser extent than sulfonylureas. • If a meal is skipped, the dose is skipped; if a meal is added, a dose is added for that meal. • taken with decreased kidney function.
Repaglinide (NovoNorm) Precautions • Longer half-life may be found with antifungals, erythromycin and clarithormycin. • Accelerated repaglinide metabolism and shortened drug effect may be found with use of rifampin, phenobarbital, carbamazepine, and troglitazone. Side Effects • Hypoglycemia (16%) • Back pain • Headache
Repaglinide (NovoNorm) Dosing • Is available in 0.5 mg, 1 mg and 2 mg dosage units. Maximum dose is 16 mg. per day. Take with meal. Number of daily doses is determined by the number of meals eaten. • Initial dose for clients not previously treated with BG lowering agents: 0.5 mg/meal Initial dose • for clients previously treated with BG lowering agents or HbA1C > 8%: 1-2mg/meal Candidates for Initial Use • Type 2 diabetes no dyslipidemia, not overweight, • with or without renal failure • fasting plasma glucose > 20 mg/dl above target
Repaglinide (NovoNorm) Contraindications • Type 1 diabetes. • Pregnancy and lactation. • Diabetic Ketoacidosis. • Impaired hepatic function. • Elderly, debilitated or malnourished persons. • Surgery, trauma or severe metabolic stress. • Serious illness/severe infection.
D-Phenylalanine Derivative • Nateglinide (Starlix) • Is very rapid-acting. • Stimulates insulin secretion when needed (postprandial), then allows insulin concentrations to return to baseline. • If a meal is skipped, the dose is skipped; if a meal is added, a dose is added for that meal. Side Effects • Hypoglycemia (2.4%) • Dizziness (3.6%), Weight gain of < 1 kg • Contraindications • Type 1 diabetes • Pregnancy and lactation • Diabetic Ketoacidosis
Nateglinide (Starlix) • Dosing • Is available in 60 mg and 120 mg tablets. • Typical dose: 120 mg taken just before meals. (60 mg tid can be used for those near their HbA1C goal). • Not recommended for combination with a sulfonylurea or NovoNorm. • Candidates for Initial Use • Type 2 diabetes with the ability to produce insulin. • significant postprandial hyperglycemia not controlled by nutrition therapy and exercise.
Type 2 SUs NOVONORM • Rapid onset (< 10 minutes) • Short time to peak (tmax: 0.7 hours) • Short half life (t½~1.0 hours)
Biguanides • Metformin (Glucophage,Cidophage) • Decreasing glucose output from the liver. Does not stimulate insulin release. • Controls blood glucose without causing hypoglycemia or weight gain in most people. A 2-5 kg weight loss is typical. • Can be used as monotherapy if diet alone does not control blood glucose. • Can be used in combination therapy when euglycemia is not achieved with the sulfonylurea alone. • Decrease in triglycerides (16%), LDL-cholesterol (8%) and total cholesterol (5%); along with an increase in HDL-cholesterol (2%). • Evaluate kidney and liver (LFT) before initiating metformin. Test creatinine and LFTs every 6-12 months while on metformin therapy.
Metformin (Glucophage) • Side Effects • Most common: GI (abdominal bloating, nausea, cramping, diarrhea, feeling of fullness) • Contraindications • Type 1 diabetes. • Pregnancy and lactation. • Hepatic dysfunction • Renal dysfunction with serum creatinine >1.5 mg/dl • Over age 80 • Metformin should be temporarily discontinued in any situation that predisposes the individual to acute renal dysfunction including: • *Cardiac collapse • *Acute myocardial infarctions • *Acute exacerbated congestive heart disease. • *Use of iodinated contrast media
Metformin (Glucophage) Dosing • Metformin (Glucophage) is available in 500 mg ,850 mg and 1000 dosage units. • Start at 500 mg per day or 500 mg bid Increase by 500 mg per day every 2 weeks up to a maximum effective dose of 2000 mg. • Candidates for Initial Use • Type 2 diabetes, dyslipidemia, • obesity or genetic factors favoring insulin resistance, • fasting plasma glucose > 20 mg/dl above target.
Alpha Glucosidase Inhibitors • Acarbose (Glucobay) • Delays carbohydrate digestion and slows absorption. • Does not cause hypoglycemia. • Approved for use in type 2 diabetes to treat postprandial hyperglycemia. • not effective in the treatment of fasting hyperglycemia. • Should not be used if the patient is using lispro (Humalog) or Novolog (Aspart) insulin--mechanism of action is similar. • Should also not be used with metformin--severe GI side effects may occur. • Check serum transaminase level every 3 months during the first year and then periodically. If elevated, discontinue acarbose. • May be used alone or in combination therapy
Acarbose (Glucobay) • Side Effects • Most common: GI (abdominal pain, diarrhea, flatulence) • Increased serum AST or ALT (Acarbose doses > 200 mg tid) • Contraindications • Safety not tested for pregnancy or lactation • Chronic intestinal problems or diseases present (inflammatory bowel disease, colonic ulceration, obstructive bowel disease and gastroparesis). • severe liver and renal disease (creatinine > 2.0).
Thiazolidinediones • Pioglitizone (Glustin) and Rosiglitizone (Avandia) • Decreases insulin resistance and increases glucose uptake in muscle and adipose tissue. • Useful in patients with renal dysfunction or other conditions in which metformin is contraindicated. • Precautions • Liver function tests should occur with Glustin and Avandia. Check serum transaminase levels (ALT) prior to starting therapy, every 2 months during the first year, and then periodically. • Do not use if ALT exceeds 2.5 X upper limit of normal or if active liver disease is present. If ALT exceeds 3 X upper limit of normal during treatment Discontinue drug • Check liver function immediately if signs of hepatic dysfunction occur (nausea, vomiting, abdominal pain, fatigue, anorexia)
Pioglitizone (Glustin) and Roisglitizone (Avandia) • Side Effects • Increased hepatic enzymes • Weight gain • Plasma volume expansion • Edema • May make oral contraceptive less effective • Contraindications • Pregnancy or lactation • Children • Hepatic dysfunction • NYHA Class III or IV Heart Failure • Pre menopausal anovulatory women with insulin resistance.
Pioglitizone (Glustin) • Dosing • Approved for monotherapy or in combination with sulfonylurea, metformin or insulin • Available in 15 mg, 30 mg tablets. • Initial starting dose in monotherapy or combination therapy is 15 mg or 30 mg once daily, taken without regard to meal. • Maximum dose is 45 mg once per day. • If used with insulin, insulin may need to be decreased by 10-25% if patient reports hypoglycemia. • Sulfonylurea dose may need to be lowered if hypoglycemia occurs. • Some studies showed a 5-26% decrease in triglycerides and a 6-13% increase in HDL-cholesterol.
Roisglitizone (Avandia) • Dosing • Approved for monotherapy or for use with sulfonylurea, metformin or insulin • Avandia is available in 4 mg tablets. • Usual starting dose is 2 mg/day - single dose or divided into 2 doses/day. • Max dose 8 mg/day. 4 mg bid is more effective than 8 mg once a day. • Studies show small increases in HDL-cholesterol and LDL-cholesterol.. • Candidates for Initial Use • Type 2 diabetes • obesity or genetic factors favoring insulin resistance • fasting plasma glucose > 20 mg/dl above target
Insulin Therapy • Type 2 Diabetes • If blood glucose >126 mg/dl fasting and over 200 mg/dl postprandial after trying meal planning, activity, and weight loss, medications insulin is indicated. • Some patients may need to be started on insulin immediately, especially if they have unexplained weight loss and severe hyperglycemia. • Starting insulin • Lean patients: 15 units NPH or Lente per day • Obese patients: 20-30 units of NPH or Lente per day • Doses can be increased 2-5 units every 3-4 days, depending on blood glucose levels. • Some may need over 100 units of insulin per day to control blood glucose.
Insulin Therapy • Type 1 Diabetes • Starting Insulin Doses • Start Dosage Eventual Dosage (u/kg/day) (u/kg/day) Prior to puberty 0.2 - 1.0 0.5 - 1.0 Pubertal 0.3 - 1.5 0.8 - 1.5 Post pubertal 0.3 - 1.2 0.8 - 1.2. • Initial dose • Higher dose lower dose • Obese Thin & Well • Long duration of symptoms Recent illness • Extreme hyperglycemia Minimal hyperglycemia • Just post-DKA episode No DKA, minimal ketones • Minimal symptoms
Insulin Therapy • General roles • Generally 0.5-1 unit per kg. of body wt. (adolescents often need closer to 1 unit per kg.) • Two doses: 2/3's of the total dose in the AM and 1/3 in the evening. • Evening NPH can be delayed until bedtime snack to counteract the "Dawn Phenomenon", especially if large pre-supper NPH dose is causing nocturnal hypoglycemia. • A "honeymoon phase" may occur within a few weeks after diagnosis and last for several months, which reduces insulin needs to about 0.1-0.3 units per kg., and only one shot per day may be required.
Insulin Therapy • Twice - Daily Insulin Regimens • Fasting hyperglycemia:Check 3 a.m. blood glucose. If it is >70 mg/dl, increase evening NPH by 10% (Also, before increasing dose, changing NPH dose from presupper to prebed may help lower AM glucose.) • Fasting hypoglycemia(and low 3 a.m. blood glucose): Reduce evening NPH by 15%. • Elevated midmorning or prelunch blood glucose: Increase AM by 10%. • Prelunch blood glucose <70 mg/dl: Reduce AM R by 15%. • Presupper blood glucose higher than desired:Increase AM NPH by 10%.
Insulin Therapy • Elevated evening blood glucose (>180 mg/dl after supper and prebed over 120 mg/dl after bedtime snack for 3 days): Increase presupper R insulin by 10%. • Also, make certain that • the insulin injection is given 30 minutes before meal if using Regular insulin. • It may also be useful to check technique and injection sites used. • Intensive Therapy • blood glucoses kept as close to normal levels as possible resulted in the development of significantly fewer complications. • Intensive therapy is not for extremely young children and infants because of the risk of permanent damage from hypoglycemic events.
Pharmacokinetic Profiles of Human Insulin and Insulin Analogues.